Are LVADs Ready To Be Mainstream? Joseph G. Rogers, MD Associate Professor of Medicine Duke...
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Transcript of Are LVADs Ready To Be Mainstream? Joseph G. Rogers, MD Associate Professor of Medicine Duke...
Are LVADs Ready To Be Mainstream?Joseph G. Rogers, MDAssociate Professor of MedicineDuke University Medical Center
J105-0311
Address a large patient population
Established safety and efficacy
Have a proven track record of clinical success
Have an acceptable risk / reward tradeoff
Mainstream Therapies
Addressing An Unmet Need
The VAD patient population is approaching 100,000 in the United States alone.
US population1
Target population (35-74 age cohort)1
Diagnosed CHF population2
All ages
35-74
NYHA Class IIIB and IV3 in 35-74 age cohort
Comorbidities estimated in this cohort
Target VAD patient population (35-74 years)
301,000,000
139,100,000
5,520,000
3,744,000
374,400
(280,800)
93,600
1 US Census Bureau Statistics (2007)2 Heart and Stroke Statistics, American Heart Association
3 Cardiovascular Round Table research and analysis, The Advisory Board company (2009)
Medical therapy alone can be a poor long-term treatment option for many in the more advanced stages of heart failure.
Four major publications show the mortality risk associated with NYHA Class IV heart failure is high, with a 1-year mortality between 60 and 94 percent.1-4
Heart Failure Has A High Mortality Rate Similar To Aggressive Malignancies
Class IV heart failure patients treated with medical therapy alone have mortality rates similar to or greater than aggressive forms of cancer.5
1 Rose, Gelijns, Moskowitz, et al. NEJM. 345:1435-43, 2001. 2 Rogers, Butler, Lansman, et al. J Am Coll Cardiol. 50:741-47, 2007.
3 Hershberger, Nauman, Walker, et al. J Card Fail. 22:616-24, 2003.4 Gorodeski, Chu, Reese, et al. Circ Heart Fail. 2:320-24, 2009.
5 Data on file. Pleasanton, Calif: Thoratec Corp.
HeartMate II is the first and only FDA-approved continuous flow device for both Bridge-to-Transplantation (BTT) and Destination Therapy (DT).
HeartMate II®—A Proven Adjuvant Therapy For Advanced-Stage Heart Failure
Bridge-to-Transplantation
Non-reversible left heart failure
Imminent risk of death
Candidate for cardiac transplantation
Destination Therapy
NYHA Class IIIB or IV heart failure
Optimal medical therapy 45 of last 60 days
Not a candidate for cardiac transplantation
For inpatient and outpatient use
HeartMate II—Design Features
-
Optimized blood flow
Low thrombosis risk
Low anticoagulation requirements
Reliability
Received European CE Mark in November 2005
Received FDA approval for BTT in April 2008
Received Health Canada approval in May 2009
Received FDA approval for DT in January 2010
Distributed throughout Asia and Australia
HeartMate II—Widespread Approval And Adoption
FDA approval for BTTApril 2008
European CE MarkNovember 2005
FDA approval for DTJanuary 2010
More than 6,000 patients, spanning over 6,000 patient years across 254 centers worldwide, have now been implanted with the HeartMate II LVAD*
Patients supported 2 years: 700
Over 60 patients supported 4 or more years
Longest support duration: 6 years
Smallest patient: 1.1 BSA
Largest patient: 3.2 BSA
Age range: 11–87
HeartMate II—Most Widely Used, Proven Efficacious, and Durable in Broad Patient Population
*As of January 13, 2011
HeartMate II has an unparalleled number of peer-reviewed published studies in highly regarded publications including NEJM and JACC.
Data featuring HeartMate II has been published in more than 120* peer-reviewed articles including:
3 New England Journal of Medicine
6 Journal of American College of Cardiology
5 Circulation
35 Journal of Heart and Lung Transplantation
11 Annals of Thoracic Surgery
10 Journal of Thoracic Cardiovascular Surgery
HeartMate II—Peer-Reviewed Publications
*As of January 2011
Improvements With BTT Results Over Time
Miller, Pagani, Russell, et al. NEJM. 357:885-96, 2007.Pagani, Miller, Russell, et al. JACC. 54:312-21, 2009.
Starling, Naka, Boyle, et al. JACC, in press 2010.
n = 133 n = 281 n = 169
HeartMate II—Contemporary BTT Outcomes
The HeartMate II BTT post-approval study was initiated to assess outcomes in a broader patient care environment outside of a clinical setting, representing real life situations.
HeartMate II Group
First 169 consecutive HeartMate II patients enrolled in INTERMACS listed, or likely to be listed, for transplant
77 centers enrolled patients from April to August 2008, and were followed for at least 1 year post-implant
Endpoints
The primary endpoint was survival, and secondary endpoints included adverse events reported upon occurrence and functional status using the 6-minute walk test and EuroQoL scale—determined at baseline and 3, 6, and 12 months post-implant
Kirklin JK, Naftel DC, Kormos RL, et al. Second INTERMACS annual report: more than 1,000 primary left ventricular assist device implants. J Heart Lung Transplant. 2010;29:1-10.
The majority of enrolled patients were noted to be INTERMACS 1 or 2.
HeartMate II Post-Approval Study Patient Demographics
Operative 30-day survival was 96% and patients achieved 90% successful outcomes at 6 months and 85% at 1 year.
HeartMate II Post-Approval Study Actuarial Survival
Starling, Naka, Boyle, et al. JACC, in press 2010.
As demonstrated by the EuroQoL instrument, HeartMate II patients experienced early and sustained improvement in quality of life over the course of follow-up, with scores doubling at 12 months post-implant.
HeartMate II Post-Approval Study Quality Of Life
Starling, Naka, Boyle, et al. JACC, in press 2010.
HeartMate II Adverse Event Rates From The BTT Post-Approval Study
Events per patient year.
Pagani FD, Miller LW, Russell SD. Extended mechanical circulatory support with a continuous-flow rotary left ventricular assist device. J Am Coll Cardiol. 2009;54:312-21.
Starling, Naka, Boyle, et al. JACC, in press 2010..
The HeartMate II post-approval study demonstrated low adverse event rates for stroke and RV failure.
Stroke and RV failure rates have improved from the HeartMate II pivotal clinical trial.
Destination Therapy Pivotal Trial
Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361(23):2241-51.
The pivotal HeartMate II
Destination Therapy trial
demonstrated significant
improvements in outcomes
compared to randomized
patients with pulsatile LVADs
68% survival at 1 year
58% survival at 2 years
Survival In The Destination Therapy Pivotal Trial
Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361(23):2241-51.
Fang JC. Rise of the machines–left ventricular assist devices as permanent therapy for advanced heart failure. N Engl J Med. 2009;361(23):2282-84.
Destination Therapy Trial CAP: Overview And Baseline
Park SJ. AHA Scientific Sessions, November 2010.
More than 500 additional DT patients have been enrolled under a continued access protocol (CAP).
Mid-trial patients did not vary in baseline characteristics
Improvements In DT Survival
Patients enrolled in the mid-trial experienced better survival.
* P value adjusted for body surface area Park SJ. AHA Scientific Sessions, November 2010.
Park SJ. AHA Scientific Sessions, November 2010.
Hemorrhagic stroke > 50% reduction
0.03 events per patient year
Device-related infections > 35%
reduction
0.27 events per patient year
Sepsis > 25% reduction
0.27 events per patient year
DT CAP Trial Shows Significant ReductionsIn Adverse Events
* p < 0.05** p < 0.01
HeartMate II therapy stroke rates are similar to other commonly accepted cardiac surgical procedures such as CABG and valve procedures.
Stroke Rates Similar To Other Cardiac Surgical Procedures
McKhann GM, Grega MA, Borowicz LM, et al. Stroke and encephalopathy after cardiac surgery - an update. Stroke. 2006;37:562-71.Boyle AJ, Russell SD, Teuteberg JJ, et al. Low thromboembolism and pump thrombosis with the HeartMate II left ventricular assist device:
analysis of outpatient anti-coagulation. J Heart Lung Transplant. 2009;28:881-87.
Incidence of stroke by cardiac surgical procedure(data collected at Johns Hopkins from 2001 – 2004)
DT CAP Trial Functional Class Improvements
Park SJ. AHA Scientific Sessions, November 2010.
n = 266 n = 191 n = 158 n = 125 n = 67
All patients were Class IIIB or IV at baseline.
DT CAP Trial Quality Of Life Improvements
74
30
225 m
343 m
Park SJ. AHA Scientific Sessions, November 2010.
A range of referral criteria assessments and scoring systems can be utilized to define the right moment to screen a patient for a HeartMate II implant.1
Appropriate timing for referral is when a patient presents in Class IIIB or IV heart failure and has more than one of the functional or laboratory risk factors.
Improved Timing Of Patient Referral For Evaluation
Functional AssessmentInability to walk one block without shortness
of breathIntolerant or refractory to ACE inhibitor,
angiotensin receptor blockers, or beta-
blockersOne heart failure-related hospital admission
in the past 6 months2
CRT nonresponderHigh diuretic dose (e.g., 120 mg/d
Furosemide)
Lab AssessmentSerum sodium < 136 mmol/LBUN > 40 mg/dL or Serum Creatinine > 1.8
mg/dLHemotocrit < 35%
1 Russell SD, Miller LW, Pagani FD. Advanced heart failure: a call to action. Congest Heart Fail. 2008;14:316-21.2 Teuteberg J, Lewis E, Nohria A, et al. Characteristics of patients who die with heart failure and low ejection fraction in the new millennium. J Card Fail. 2006;12(1):47-53.
In Summary
HeartMate II:
Compelling data from large clinical trials demonstrates efficacy
Achieved very high survival rates
BTT – 90% 6 months, 85% 1 year
DT – 74% 1 year, 64% 2 years
Superior to what is anticipated with optimal medical management
Substantial and sustained quality of life improvements
Acceptable adverse event profile
67 y/o referred for advanced heart failure therapy
Ischemic cardiomyopathy EF < 20% with LVEDD = 7.3 cm
Cath 1 month prior: 20% pLM, 100% pLAD, stent in pLCX, 50% stenosis pOM1,
60% pRCA with diffuse 50% stenosis throughout. Patent LIMA to LAD, patent SVG
to PDA with 50% proximal stenosis
Thallium: anterior infarct, no ischemia
ICD
Co-morbidities: HTN, DM, hyperlipidemia
Case Study
Hospitalized once in past 6 months Progressive exertional dyspnea and fatigue (e.g., unable to climb 1 flight
of stairs without dyspnea or unhappy with current level of functionality) Occasional nocturnal dyspnea No edema Appetite adequate and no weight change No ICD shocks Meds: ASA 81 mg daily, Clopidogrel 75 mg daily, Furosemide 40 mg
daily, Lisinopril 10 mg daily, Metoprolol Tartrate 25 mg twice daily,
Simvastatin 20 mg daily, Spironolactone 25 mg daily
Case Study
Examination
HR=92, BP=96/78
Clear lungs
Depressed carotid upstrokes, JVP=12, RRR, No S3 or murmur
Trace LE edema
Labs: Sodium=134mmol/L, BUN=12 mg/dl, Cr=0.8 mg/dl,
BNP=436pg/ml, Albumin=3.5 g/dl
Case Study
Level 1 CPX Results 2 minutes and 37 seconds, Ekelund protocol
Peak HR=148, Peak BP=102/71
RER=1.16
Peak VO2=11.6 ml/kg/min (49% predicted)
VE-VCO2 Slope=49.8
Case Study